Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Significance

Fatigue is a significant health concern for many populations across the life course including older adults and individuals with chronic illnesses such as cancer. Fatigue is the most common reason for restricting activity in previously functional community-dwelling older adults. Cancer-related fatigue (CRF) is recognized as one of the most common symptoms in patients receiving treatment for cancer, often persisting beyond the conclusion of active treatment and through the end of life. Longitudinal and comparative studies indicate that fatigue may also be a significant problem for cancer survivors, with many survivors reporting fatigue scores higher than that of an age-matched general population.

We have made limited progress in delineating the pathophysiology and optimal treatment of fatigue, and there is emerging evidence to suggest that fatigue may not be a unitary phenomenon. Current therapeutic approaches targeting fatigue (for example exercise, mindfulness-based stress reduction) are non-specifically applied to a vaguely defined symptom, and treatment responses have been difficult to capture. Innovations in the conceptualization and measurement of fatigue are needed to (i) identify its distinct domains; (ii) distinguish it from related phenomena such as depression, diminished cardiopulmonary reserve, or sarcopenia; (iii) expand our mechanistic understanding of fatigue; and (iv) identify novel targets for its treatment.

The empiric work stimulated by this FOA will enhance research examining the characteristics, underlying mechanisms, and optimal treatment of fatigue in older adults, including those with cancer. Measurement of fatigability will complement currently used measures of fatigue perceptions, muscle strength, and daily activity, and could reveal subgroups of fatigued individuals who experience performance deterioration or increased perceived exertion in response to activities that pose a demand. Valid measurement of fatigability and an expanded conceptual understanding of its relationship to fatigue have the potential to reveal important underlying mechanisms of fatigue. Such work can also yield a responsive new endpoint beyond simple perceptions of fatigue severity to measure therapeutic response in trials of new treatment approaches for fatigue.

Fatigability vs. fatigue

Fatigue is a symptom, defined in this FOA as a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual or desired activities . The mainstay of fatigue measurement has been self-report; more than 25 self-report measures of fatigue are in use. Such tools capture individual perceptions (severity, distress, interference, or bother) of the sensation of fatigue; however they neglect the important context of physical and functional performance demands in daily life.

Fatigability, however, is not a symptom; rather, fatigability is defined in this FOA as a characteristic describing an individual’s susceptibility to experiencing fatigue for a given quantifiable demand. Fatigability is an attribute reflecting the magnitude of fatigue that an individual experiences as a function of the magnitude of demand he/she undertakes. Fatigability in this FOA is operationally defined at the individual or "whole person" level; that is, in relation to functional limitations or disabilities as articulated in Nagi’s disablement model. Functional limitations refer to restrictions in basic physical or cognitive actions, such as walking, climbing stairs, or speaking, and disabilities refer to inability to perform these actions in specific contexts of daily life (e.g., home, work, recreation). In contrast, measurements below the whole person level, such as organ system, tissue, or cellular levels (e.g., decline in muscle force with repeated contractions), lie outside the scope of this FOA.

The distinction between fatigability and fatigue is important because of a fundamental confounder in most fatigue measures: self-pacing. Consider, for example, two 72-year-old women. Both report moderate fatigue on a validated self-report scale, yet the physical and functional performance demands of their daily lives are markedly different. One woman continues full-time employment, walks 4 miles daily, lives in a two-story house, and has rich social interactions; the other individual is retired, resides in an assisted living facility with an elevator, and prefers quiet and sedentary activities. While self-reported fatigue levels are similar, the intensity and duration of activity provoking their fatigue likely differ substantially. The first individual has lower fatigability to achieve her moderate fatigue, she must engage in substantial and robust daily activity. The second individual has higher fatigability it does not take much daily activity to become moderately fatigued. Isolated measurement of fatigue perception provides incomplete information to distinguish and treat these two individuals. Each may titrate the pace of her usual activities to maintain fatigue levels within tolerable limits. Differences in usual activity levels, despite similar experiences of fatigue, likely represent different levels of endurance, strength, and efficiency, which, in turn, reflect different underlying physical and cognitive reserves. Thus, fatigability is an inherent characteristic of an individual that is likely to be stable over weeks or months, in contrast to fatigue, which may fluctuate considerably over minutes or hours. Empirical evidence supports the assertion that fatigability and fatigue are distinct constructs.

Understanding fatigability as an outcome, distinct from the outcome of fatigue, may have a variety of research and clinical implications. For example, understanding fatigability may help to explain the observation that self-reported fatigue remains stable or even decreases with advancing age in cross-sectional studies. Ascertainment of fatigability may also provide an explanation for the observation that, across chronically ill populations, younger individuals tend to report more fatigue compared with their older counterparts. In both cases, such individuals may modify the type or pace of their activities to keep their fatigue levels bearable. Thus, fatigability can account for variations in underlying activity that influence the severity of fatigue symptoms, which is not captured by measurement of daily activity alone, as doing so cannot disentangle lifestyle choices or behavioral changes that result from self-pacing or disability.

Measurement of fatigability may also have implications for the development of therapeutics for fatigue. An intervention that results in unchanged levels of fatigue may, at first glance, appear ineffective, but if the intervention leads to increased levels of usual activity, the intervention may have, in fact, improved underlying physiology. Conversely, an intervention that results in decreased fatigue may appear effective, but if usual activity levels decrease concomitantly, then the intervention more likely led to adjustment or accommodation to the fatigue experience rather than a true change in physiology. Thus, a valid measure of fatigability could facilitate the development of interventions for fatiguing conditions, where few effective treatments currently exist.

Fatigability may be conceptualized in two forms: perceived fatigability and performance fatigability. Perceived fatigability is a characteristic based on an individual’s self-reported feeling of tiredness as a function of the duration and intensity of a demand task or activity. Performance fatigability is a characteristic based on the decline in force, endurance, power, speed, reactivity, or accuracy of performance of a given activity or task.

To date, measurement approaches to fatigability have been quite limited. This may be in part because fatigability, as a latent (i.e., unobservable) construct, can be revealed only in the context of a physical or cognitive demand. Thus, a measure of fatigability should assess both 1) the intensity and duration of one or more physical or cognitive demands, and 2) the accompanying level of perceived fatigue, perceived effort, or decrement in performance.

Within these constraints, a variety of approaches may be taken to develop valid, reliable, and responsive measures of fatigability under this FOA. Approaches to fatigability measurement include but are not limited to performance-based measures of function and instrumented (e.g., sensor, mobile health data) measures of physical activity and functional performance. Common to all approaches, however, is the combination of a measure of fatigue with a measure of demand. Please refer to www.nia.nih.gov/research/dgcg/fatigability-rfa for more information about potential approaches.

This FOA invites applications to develop and evaluate measures of fatigability. This FOA is not intended to support the addition of one more instrument to the extensive assortment of existing fatigue measures. Rather, this FOA is intended to substantially advance the science of disability measurement through development of a qualitatively different construct -- fatigability -- by addressing the inherent problem of self-pacing that confounds most measures of fatigue.

Target populations include: (a) individuals with fatigue attributable to one or more underlying diseases or conditions, (b) individuals with fatigue without any apparent underlying cause or subclinical conditions (idiopathic fatigue), and (c) healthy individuals (as comparators). This FOA includes populations across the lifespan, particularly older adults.

Measures developed for this FOA may be adaptations of existing tools or de novo instruments. Both quantitative and qualitative methodologies may be appropriate depending on the type of study proposed. In general, new data collection is expected, though secondary analyses of existing data may be performed where appropriate.

This FOA supports research activities that include, but are not limited to, one or more of the following:

• Development of a conceptual model of fatigability through systematic literature reviews; convening of focus groups comprised of patients, clinicians, content experts, and other relevant contributors and stakeholders; concept analyses; and other activities necessary to lay a solid conceptual groundwork.
• Reliability testing.
• Testing construct, content, and criterion validity. Comparison with established functional measures is particularly important.
• Testing for measurement invariance across age, gender, race/ethnicity, and distinct levels of cardiopulmonary fitness or functional capacity.
• Demonstration of feasibility, responsiveness to change, and minimum clinically detectable change.
• Validation in specific populations of individuals; e.g., older adults, patients with cancer, cancer survivors, and persons with multiple chronic conditions (MCCs). Studies should consider the potential for factors such as pain, cachexia, sarcopenia, and other related conditions to confound measurement in these populations.
• For studies that will involve patient-reported outcomes (PROs), the following activities are especially important:
  • Characterization of factors that influence how subjects arrive at their self-reported evaluations of fatigability, such as time horizon, choice of comparator, prominence of past experiences, and other response heuristics.
  • Development and refinement of language to ensure readability, appropriateness of content to life stage and functional capacity (for example, to avoid floor/ceiling effects), consistency of meaning, appropriateness of stems, and other item characteristics.
  • Optimization of readability versus accuracy. Intensity, duration, or other characteristics of activities should be worded in sufficient detail to permit adequate inter-individual comparisons. Applicants should conduct studies to determine the optimal balance between feasibility of the instrument for the settings in which it is intended, and its reliability in those settings.
  • Adjustment for confounding by mood disturbances, impaired sleep, and pain.

Criteria for responsiveness to this FOA

Applications will be reviewed administratively and assessed for responsiveness to this FOA. Evaluations of responsiveness will include the following considerations:

• Applications that operationalize fatigability at the level of muscle fibers, single muscles, or muscle groups will be considered non-responsive (e.g., repeated hand or foot contractions). This FOA is intended to support studies on fatigability at the level of the individual as described above.
• Applications that conceptualize fatigability as a symptom will be considered non-responsive. Fatigability in this FOA is an inherent attribute or characteristic of an individual, not a symptom.

Grantee meetings are anticipated during each year of award. These meetings will be an opportunity for awardees to share information about their respective scientific approaches, discuss challenges encountered in their measure development activities, and explore opportunities for collaboration with each other where possible.

A webinar for prospective applicants is planned to provide prospective applicants the opportunity to receive information and ask questions about the scientific scope of this announcement and technical details for applying. Please see www.nia.nih.gov/research/dgcg/fatigability-rfa for information about timing and access.

Applicants are encouraged to explore the resources available through the NIH Patient Reported Outcomes Medical Information System (PROMIS) (http://www.nihpromis.org), NIH Toolbox (http://www.nihtoolbox.org), and NIH Quality of Life Outcomes in Neurological Disorders (Neuro-QOL) (www.neuroqol.org).

Applicants may wish to consult the NIA Population Studies Database (http://nihlibrary.ors.nih.gov/nia/ps/niadb.asp) for existing longitudinal studies that may be appropriate for secondary analyses and/or ancillary studies in support of fatigability conceptual development.

This FOA does not specify a particular age cutoff to demarcate older from younger adults. Age ranges should be selected based on the questions under study; however, applicants are encouraged to involve a wide age range of older adults, including the oldest old, and a spectrum of functional abilities.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Ramesh Vemuri, PhD
Telephone: 301-402-7700
Fax: 301-402-0066
Email: VemuriR@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should include in their budget requests support for travel to annual grantees' meeting held in Bethesda, Maryland. Except in unusual circumstances, only the PD/PI may be supported by R21 funds to travel to the grantees' meeting. Applicants should budget for travel (air and/or ground) to and from Bethesda, Maryland, one night's lodging, and meals. There is no specific line item in which to list travel costs in the Modular Budget format; however, the proposed travel should be included in the budget justification section.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Applicants are strongly encouraged to address the limitations of the measure they propose. For example, applications involving patient-reported outcomes (PROs) should address the potential impact of personality, cognitions, mood, environmental context, and respondent biases in order to maximize intra- and inter-individual comparability, and incorporate efforts to demonstrate that the fatigability measure is valid, reliable and responsive in the population(s) and clinical or research setting(s) of interest. Perceived fatigability measures in which fatigue and demand are assessed in a single instrument should ascertain variability in respondents interpretations of the envisioned or recalled effort required for each demand. For example, if an item queries for the level of fatigue experienced after 15 minutes of walking, respondents may have markedly different interpretations of the intensity of that activity depending on their health status, level of aerobic conditioning, presence of disability, etc. Applicants developing a performance fatigability measure should ascertain whether performance declines are attributable to tiredness, as opposed to pain, breathlessness, or other activity-limiting symptoms.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute on Aging (NIA) and the National Cancer Institute (NCI), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the application involves patient-reported outcomes, will the investigators address the potential impact of personality, cognitions, mood, environmental context, and respondent bias? If perceived fatigability is measured in a single instrument, will the investigators ascertain variability in respondents' interpretations of envisioned or recalled effort for each demand? If a performance fatigability measure is developed, will the investigators ascertain whether declines in performance are attributable to tiredness as opposed to other symptoms?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute on Aging, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Basil Eldadah, MD, PhD
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: eldadahb@mail.nih.gov

Sandra Mitchell, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6929
Email: sandra.mitchell@nih.gov

Ramesh Vemuri, PhD
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: VemuriR@mail.nih.gov

Lesa McQueen
National Institute on Aging (NIA)
Telephone: 301-496-1472
Email: Lesa.McQueen@nih.gov

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: perryc@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.